Nicotine withdrawal is a serious obstacle to successful smoking cessation, the prevention of which forms the basis of nicotine replacement therapy. There is strong evidence that caffeine metabolism is decreased when nicotine intake is discontinued, leading to blood levels of caffeine that are double the prequit levels - without an increase in caffeine intake. Since many of the effects of excessive caffeine are similar to nicotine withdrawal it is possible that nicotine withdrawal effects-in caffeine users are exaggerated because of decreased caffeine metabolism. Caffeine-induced increases in withdrawal symptoms would likely increase the chances of smoking relapse, which would in turn increase the risk of disease. Three studies are proposed to delineate the role of caffeine in the Tobacco Withdrawal Syndrome. The first study will compare nicotine intake via smoking and nicotine polacrilex to verify that both caffeine intake and caffeine metabolism are changed equally by both methods of nicotine intake, thus verifying that nicotine (rather than some other component in the smoking process) is the cause of decreased caffeine metabolism after smoking cessation. The second study will assess nicotine dose-related changes in caffeine intake, caffeine metabolism, and nicotine withdrawal symptoms. This second study will further clarify the role of nicotine in caffeine intake and caffeine metabolism, particularly as it relates to withdrawal symptoms. In addition, the second study will evaluate whether the effect of nicotine intake on caffeine metabolism is a linear one, so that preliminary recommendations about decreased caffeine intake after smoking cessation can be made. The third study will control both nicotine and caffeine intake, with the goal of evaluating whether a specific decrease in caffeine intake concurrent with nicotine abstinence will result in less intense nicotine withdrawal symptoms. Study three will provide the information needed to make specific recommendations about whether caffeine intake should be reduced in order to decrease withdrawal symptoms during nicotine abstinence. The three studies proposed will provide definitive data on the effects of decreased caffeine intake on tobacco withdrawal symptoms, with implications for smoking relapse. Since as many as 80% of the U.S. smokers regularly use caffeine, the results of the proposed studies will apply to a wide group of smokers, and in particular those smokers who are codependent on caffeine and who want to quit smoking.